calcium aluminosilicate anti-diarrheal in treating and preventing diarrhea in patients with metastatic colorectal cancer receiving irinotecan

Conditions: Chemotherapeutic Agent Toxicity; Colorectal Cancer; Diarrhea

Summary: rationale: calcium aluminosilicate anti-diarrheal (casad) may help treat and prevent diarrhea caused by irinotecan. it is not yet known whether casad is more effective than a placebo in treating and preventing diarrhea in patients receiving irinotecan. purpose: this randomized phase ii trial is studying casad to see how well it works compared with a placebo in treating and preventing diarrhea in patients with metastatic colorectal cancer receiving irinotecan.

objectives: primary * to compare the efficacy of calcium aluminosilicate anti-diarrheal (casad) versus placebo in reducing the incidence of grade 3 or 4 diarrhea in patients with metastatic colorectal cancer receiving an irinotecan-based chemotherapy regimen. secondary * to compare stools per day in patients treated with these drugs. * to compare chemotherapy dose reductions and delays due to diarrhea in patients treated with these drugs. * to compare quality of life of patients treated with these drugs. * to compare the safety of these drugs in these patients. * to compare the incidence of grade 3 or 4 diarrhea in patients treated with these drugs. outline: this is a multicenter study. patients are stratified according to chemotherapy regimen (irinotecan hydrochloride in combination with fluorouracil and/or biologic therapy vs irinotecan hydrochloride alone). patients are randomized to 1 of 2 treatment arms. * arm i: patients receive oral calcium aluminosilicate anti-diarrheal (casad) 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. patients who develop grade 3 or 4 diarrhea and are removed from the study may receive casad for an additional 6 weeks. * arm ii: patients receive oral placebo 4 times daily for 6 weeks in the absence of disease progression or unacceptable toxicity. patients who develop grade 3 or 4 diarrhea and are removed from the study may then receive casad for 6 weeks. patients undergo quality-of-life assessment at baseline and at weeks 3, 5, and 6. after completion of study treatment, patients are followed for 30 days.

Eligibility criteria:
disease characteristics: * diagnosis of colorectal cancer * metastatic disease * scheduled to receive irinotecan hydrochloride alone or in combination with fluorouracil, cetuximab, leucovorin calcium, or other biological therapy (including bevacizumab) * no uncontrolled brain metastasis * previously treated brain metastasis allowed patient characteristics: * eastern cooperative oncology group (ecog) performance status 0-2 * absolute neutrophil count (anc) \> 1,000/mm³ * platelet count \> 100,000/mm³ * total bilirubin \< 1.5 times upper limit of normal (uln) * aspartate aminotransferase (ast or sgot) and/or alanine aminotransferase (alt or sgpt) \< 2.5 times uln (\< 5 times uln if liver metastasis is present) * alkaline phosphatase \< 2.5 times uln * creatinine clearance \> 35 ml/min * not pregnant or nursing * negative pregnancy test * fertile patients must use effective contraception * no known udp-glucuronosyltransferase 1a1 (ugt1a1) deficiency with homozygotes. * no known history of gilbert's disease * no diarrhea \> grade 1 * no serious illness or medical condition, including any of the following: * uncontrolled congestive heart failure * uncontrolled hypertension (i.e., blood pressure \> 150/100 mm hg) * uncontrolled arrhythmia * active angina pectoris * symptomatic heart disease according to new york heart association(nyha) class ii-iv * no serious uncontrolled active infection * no existing colostomy or ileostomy * not able to take and document oral study medications * no history of allergies to irinotecan hydrochloride * no history of significant neurological or psychiatric disorders that would preclude giving consent or participating in study treatment or follow up prior concurrent therapy: * see disease characteristics * prior treatment for metastatic disease allowed * at least 4 weeks since prior irinotecan * more than 2 weeks since prior chemotherapy * irinotecan alone or in combination with other chemotherapy or biologic agents allowed * more than 4 weeks since prior radiotherapy * no concurrent radiotherapy * no concurrent medication schedule that does not permit a 2-hour window between administration of calcium aluminosilicate anti-diarrheal (casad) and other medications

Keywords: diarrhea chemotherapeutic agent toxicity recurrent colon cancer recurrent rectal cancer stage iv colon cancer stage iv rectal cancer